Mouse embryonic stem cells (mESCs) are pluripotent cells that possess the ability to self‐renew and differentiate into three germ layers. Owing to these characteristics, mESCs act as important models for stem cell research and are being used in many clinical applications. Among the many cathepsins, cathepsin A (Ctsa), a serine protease, affects the function and properties of stem cells. However, studies on the role of Ctsa in stem cells are limited. Here, we observed a significant increase in Ctsa expression during mESC differentiation at protein levels. Furthermore, we established Ctsa knockdown mESCs. Ctsa knockdown led to Erk1/2 phosphorylation, which in turn inhibited the pluripotency of mESCs and induced G2/M cell cycle arrest to inhibit mESC proliferation. The knockdown also induced abnormal differentiation in mESCs and aberrant expression of differentiation markers. Furthermore, we identified inhibition of teratoma formation in nude mice. Our results suggested that Ctsa affects mESC pluripotency, proliferation, cell cycle and differentiation, and highlighted the potential of Ctsa to act as a core factor that can regulate various mESC properties.

中文翻译：

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组织蛋白酶A调节小鼠胚胎干细胞中的多能性，增殖和分化。

小鼠胚胎干细胞（mESCs）是多能细胞，具有自我更新和分化为三个胚层的能力。由于这些特性，mESCs成为干细胞研究的重要模型，并已在许多临床应用中使用。在许多组织蛋白酶中，组织蛋白酶A（Ctsa）是一种丝氨酸蛋白酶，会影响干细胞的功能和特性。然而，关于Ctsa在干细胞中的作用的研究是有限的。在这里，我们观察到在蛋白质水平上mESC分化过程中Ctsa表达的显着增加。此外，我们建立了Ctsa组合式mESC。sa敲低导致Erk1 / 2磷酸化，进而抑制mESC的多能性并诱导G2 / M细胞周期阻滞，从而抑制mESC增殖。敲低还诱导了mESCs中的异常分化和分化标志物的异常表达。此外，我们确定了裸鼠畸胎瘤形成的抑制作用。我们的研究结果表明，Ctsa影响mESC多能性，增殖，细胞周期和分化，并强调了Ctsa充当调节各种mESC特性的核心因素的潜力。